Ionic Organic Cages as Adaptable Platforms for Cooperative Tandem Catalysis

Conspectus: In biological systems, multivalent interactions orchestrate the hierarchical assembly of biomolecules into compartmentalized architectures, enabling spatial segregation and cooperative regulation of multiactive sites, thereby promoting complex reaction networks. Mimicking these assembly principles to develop biomimetic confined environments has emerged as a promising strategy for engineering highly efficient catalysts. Organic molecular cages (OMCs) possess discrete nanocavities and open windows, in which spatial confinement enables enzyme–mimetic encapsulation and stabilization of active sites; however, most research has focused on single-site catalysis. Ionic organic cages (IOCs), a charged subclass of the OMCs, incorporate charged skeletons balanced by counterions. This ionic architecture imparts pronounced biomimetic functionality, expanding their behaviors through electrostatic tunability and functional adaptability. These attributes include (1) broad solubility, particularly in aqueous media, facilitating complexation with biological sites and efficient catalysis under mild or physiological conditions; (2) tunable electrostatic microenvironments, where high-density and uniformly distributed charges of the skeleton modulate both the cavity environment and the electronic structure of encapsulated metal clusters; and (3) intrinsic multivalency, which drives hierarchical assembly and integration of multiple catalytic sites through a combination of electrostatic, covalent, and coordination interactions, recapitulating the biological compartment architecture. Ultimately, the synergy between structural mimicry and functional integration establishes IOCs as versatile biomimetic platforms.This Account highlights recent advances in IOCs as multifunctional biomimetic catalytic platforms. We first outline synthetic strategies, including direct self-assembly from charged building blocks enabled by covalent bonding, and postsynthetic modifications, including neutralization, nucleophilic substitution, and oxidation, to introduce tunable charges. These strategies allow fine control over charge density and distribution throughout the cage skeleton. We then introduce an “inside–out” framework to dissect the three defining elements of IOCs─discrete nanocavities, charged skeletons, and exchangeable functional counterions─and discuss their crucial role in endowing the IOCs with both structural and functional biomimetic characteristics. Following an “electrostatic mediation and stepwise assembly” design principle, we elucidate how multivalent interactions arising from charged skeletons and functional counterions direct hierarchical assembly, enabling the coexistence and interplay of diverse active sites (e.g., metal clusters, radicals, enzymes, and metal complexes). Special emphasis is placed on the cooperative mechanisms among multiple active sites, including compartmentalization, electron communication, and spatiotemporal regulation, which collectively underpin efficient tandem catalysis. By emulating the spatial segregation and dynamic regulation of biological systems, IOCs represent an emerging platform for designing complex catalysts that unite precision, versatility, and adaptability, offering a promising path toward artificial systems with life-like catalytic sophistication.